OBJECTIVE To investigate the risk factors for sodium valproate （VPA）-induced hyperammonemia in neurocritical patients， and to construct a risk prediction model. METHODS Clinical data were retrospectively collected from 172 neurocritical patients who received VPA treatment in the Department of Critical Care Medicine， the Fourth Affiliated Hospital of Soochow University from January 2022 to June 2025. Patients were divided into the hyperammonemia group （73 cases） and the normal group （99 cases） based on their blood ammonia levels. Univariate analysis and LASSO regression analysis were used to screen for predictive variables. Independent factors were identified through multivariate Logistic regression analysis， and a nomogram was constructed accordingly. The performance of the model was evaluated using receiver operating characteristic （ROC） curve， calibration curve， and decision curve analysis （DCA）. RESULTS Combination of univariate analysis and LASSO regression analysis screened out seven predictive variables： body mass index （BMI）≥24.0 kg/m 2 ， concomitant use of benzodiazepines， VPA blood concentration， hemoglobin， serum urea， average daily VPA dose， and albumin. Multivariate Logistic regression analysis showed that concomitant use of benzodiazepines， BMI≥24.0 kg/m 2 ， VPA blood concentration， albumin and serum urea level （with odds ratios of 1.615， 1.538， 1.623， 1.942 and 0.637， respectively； 95% confidence intervals of 1.128-2.359， 1.059-2.251， 1.112-2.431， 1.106-3.598 and 0.402-0.980， respectively） were all significantly associated with VPA-induced hyperammonemia in neurocritical patients （ P ＜0.05）. The nomogram prediction model constructed based on these variables was evaluated， showing that the area under the ROC curve was 0.810 for the test set and 0.844 for the validation set. The calibration curves closely approximated t he actual curves， and the application of this model could improve the clinical net benefit. CONCLUSIONS Concomitant use of benzodiazepines， BMI≥24.0 kg/m 2 ， high VPA blood concentration and high albumin level are independent risk factors for VPA-induced hyperammonemia in neurocritical patients， while high serum urea level is an independent protective factor. The risk prediction model constructed based on these factors exhibits good discrimination， consistency， and clinical applicability， making it applicable for predicting the risk of VPA-induced hyperammonemia in neurocritical patients.

Processing for deodorization is widely used in the production of animal-derived Chinese medicinal materials. In this study, Heracles Neo ultra-fast gas-phase electronic nose combined with chemometrics was employed to analyze the overall odor difference of Cervi Cornu Pantotrichum(focusing on that derived from Cervus nippon Temminck in this study) before and after processing. The results showed that the electronic nose effectively distinguished between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. HS-GC-MS was used to identify and quantify the volatile components in the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum, and 35 and 37 volatile components were detected in the medicinal materials and decoction pieces, respectively. The medicinal materials and decoction pieces contained 28 common volatile components contributing to the odor of Cervi Cornu Pantotrichum. The odor activity value(OAV) of each volatile component was calculated based on the olfactory threshold and relative content. The results showed that there were 17 key odor substances such as isovaleraldehyde, 2-methylbutanal, isobutyraldehyde, hexanal, and methanethiol in the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. All of them had bad odor and were the main source of the odor of Cervi Cornu Pantotrichum. The results of principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) showed that there were significant differences in volatile components between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. Based on the thresholds of P<0.05 and Variable Importance in Projection(VIP)>1, 21 differential volatile odor components were screened out. Among them, isopentanol, isovaleraldehyde, 2-methylbutanal, n-nonanal, and dimethylamine were the key differential odor compounds between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. The odor compounds and their relative content reduced, and some flavor substances such as esters were produced after processing with wine, which was the main reason for the reduction of the odor after processing of Cervi Cornu Pantotrichum.
Odorants/analysis* ; Electronic Nose ; Gas Chromatography-Mass Spectrometry/methods* ; Animals ; Volatile Organic Compounds/analysis* ; Deer ; Drugs, Chinese Herbal/chemistry*

Pediatric rheumatic diseases are a group of complex chronic inflammatory disorders， mainly including juvenile idiopathic arthritis， diffuse connective tissue diseases， systemic vasculitis， and autoinflammatory diseases. Liver involvement is quite common in pediatric rheumatic diseases. In most cases， pediatric rheumatic diseases with liver involvement manifest as varying degrees of abnormal liver enzymes or hepatomegaly and may not have significant liver parenchyma lesions， and such diseases rarely progress to liver decompensation. Only a few children with rheumatic diseases may develop severe liver lesions. Liver involvement in children with rheumatic diseases may be caused by the primary disease itself or concurrent autoimmune liver diseases， but secondary factors are more common， including drug-induced liver damage caused by drugs used to treat rheumatic diseases， viral hepatitis， and fatty liver disease. This article summarizes liver involvement in pediatric rheumatic diseases， in order to provide a reference for the etiological analysis， diagnosis， and treatment strategies of liver involvement in pediatric rheumatic diseases.

Objective:To investigatetheclinicalefficacy and satetyoflaparoscopic abdominoperineal resection with pelvicperitoneum colsure for low rectal cancer.Methods:A comprehesive search was conducted across multiple da-tabases,including the Cochrane Library、PubMed、Embase、CBM、VIP、CNKI、and WanFang Data,focusing on studies re-lated to pelvic peritoneum colsure(PPC)-oriented laparoscopic abdominoperineal resection from database inception to July,2024.Then,meta-analysis was performed using RevMan 5.3 software.Results:A total of 12 studies involving 999 patients were included.The results showed that there was no significant difference in intraoperative blood loss.The laparoscopic pelvicperitoneum colsure takes a longer time,with a statistically significant difference(WMD=12.37,95%CI=2.27～22.46,P=0.02),but the postoperative exhaust time and hospitalization time are shorter,with a statistically significant difference(WMD=0.40,95%CI=0.07～0.72,P=0.02;WMD=-2.36,95%CI=-3.33～-1.38,P＜0.00001).In terms of postoperative complications,the overall complication rate was higher in the group that did not undergo pelvic-peritoneum colsure,with a statistically significant difference(OR=0.12,95%CI=0.08～0.18,P＜0.00001).The incidence of postoperative intestinal obstruction,perineal incisional hernia,pelvic effusion infection,and radiation enteritis was higher,and the differences were statistically significant(OR=0.24,95%CI=0.13～0.45,P＜0.00001,OR=0.23,95%CI=0.11～0.49,P=0.0001,OR=0.27,95%CI=0.14～0.51,P＜0.0001,OR=0.24,95%CI:0.07～0.81,P=0.03).Conclusion:In lapa-roscopic abdominoperineal resection,closing the pelvicperitoneum has lower postoperative complications,shorter post-operative exhaust time and hospitalization time,and longer operation time,which has better clinical efficacy and safety.

Objective To compare the effects of different exercise acclimatization(EA)durations on liver injury and inflammatory response in mice with exertional heatstroke(EHS).Methods A total of 168 male C57BL/6 mice were randomly assigned to four groups using a random number table:no exercise acclimation group(EA0W,n=54),1-week exercise acclimation group(EA1W,n=54),2-week exercise acclimation group(EA2W,n=54),and blank control group(n=6).The blank control group did not undergo acclimatization training or EHS modeling.The EA1W and EA2W groups underwent daily 2-hour exercise training at a speed of 10 m/min in an environment maintained at(26.0±0.5)℃for 1 and 2 weeks,respectively,followed by a 2-day rest after training completion.EHS modeling was performed in mice of EA0W,EA1W,and EA2W groups through running at 10 m/min under controlled environmental conditions(39.5℃ambient temperature,65%relative humidity).The modeling endpoint was defined as loss of consciousness accompanied by a core body temperature≥42.7℃.All modeling procedures were systematically documented.Following modeling,18 mice from EA0W,EA1W,and EA2W groups underwent 24-hour survival analysis.Blood samples from the abdominal aorta and liver tissues were collected at 6,12 and 24 hours post-modeling(6 mice per time point for each group).Plasma levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and creatine kinase(CK)were quantified.Interleukin(IL)-1β and IL-6 concentrations were determined using enzyme-linked immunosorbent assay(ELISA).Liver tissue specimens underwent hematoxylin-eosin(HE)staining and pathological scoring.Results The EHS model was successfully established in all EA groups.When all mice in EA0W group developed EHS(65 min after the modeling initiation),the incidence rates in EA1W and EA2W groups were 50.0%and 22.2%,respectively,with a statistically significant difference between EA0W group and the latter two groups(P<0.05).When all mice in the three groups developed EHS,the time to EHS onset was significantly longer in both EA1W and EA2W groups compared to EA0W group,with EA2W group showing a longer onset time than EA1W group(P<0.05).Survival analysis revealed a significantly higher 24-hour survival rate in EA2W group(61.1%)compared to EA0W group(33.3%)(P<0.05),while no significant difference was observed between EA1W group and the other two groups(P>0.05).The levels of IL-1β,IL-6,and CK were highest at 6 h post-modeling in all EA groups(P<0.05),and liver injury was most severe at 12 h post-modeling(P<0.05).Compared to EA0W group,the levels of ALT,AST,and IL-1β,as well as liver pathology scores,were significantly lower at 12 h post-modeling in both EA1W and EA2W groups(P<0.05),with EA2W group showing significantly lower ALT and AST levels,as well as liver pathology scores than EA1W group(P<0.05).At 6 h post-modeling,CK levels were significantly higher in EA1W and EA2W groups compared to EA0W group(P<0.05),with EA2W group exhibiting higher CK levels than in EA1W group(P<0.05).Conclusions Exercise acclimation helps reduce the incidence of EHS.Following EHS onset,the survival rate of exercise-acclimated mice is higher than that non-acclimated mice,with a significantly higher survival rate in mice acclimated for 2 weeks compared to non-acclimated mice.However,no significant difference in survival rate is observed between mice acclimated for 1 week and non-acclimated mice.Additionally,exercise acclimation for 2 weeks is more effective in reducing liver injury and inflammatory responses compared to 1-week acclimation.

Objective To develop nanobodies with broad-spectrum reactivity,specificity,and high sensitivity that can be used for detecting multiple subtypes of influenza A virus,and to establish a nanobody-based enzyme-linked immunosorbent assay(ELISA)method.Methods Gene sequences of twelve nanobodies against influenza A virus were retrieved from the National Center for Biotechnology Information(NCBI)and nanobody databases.The nanoantibodies were prepared using molecular biological techniques including gene synthesis and recombinant expression.The binding activity,specificity,sensitivity,and affinity of these nanobodies were determined by ELISA screening and Gator affinity analysis.A double-antibody sandwich ELISA assay was established by combining the selected nanobody with a traditional mouse monoclonal antibody.Results Twelve nanobodies were expressed and purified.Two nanobodies capable of binding to multiple subtypes of influenza virus including H1,H3,H5,H7,and H9 were obtained and designated as VHH54 and KV108.Both nanobodies showed no cross-reactivity with other respiratory virus antigens.Furthermore,the KV108 nanobody exhibited the highest binding affinity,with a dissociation constant of 5.94×10-9mol/L for the influenza virus nucleoprotein(NP),and the lowest detection concentration for the NP antigen reached 0.00064 μg/mL.The double-antibody sandwich ELISA,using a combination of KV108 and a mouse monoclonal antibody,could sensitively detect the five common subtypes of influenza A virus(H1N1,H3N2,H5N1,H7N9,and H9N2).The lowest detection limit reached 110-403 PFU/mL,which was higher than that of the commercial colloidal gold kitfor influenza virus detection.Conclusion This study has identified a nanobody KV108,which is capable of binding to multiple subtypes of influenza virus,and established a nanobody-based ELISA method that can detect multiple subtypes of influenza A virus.This study can facilitate the development of nanobody-based influenza detection technologies.

Objective: To compare the transcriptomic profiles between three distinct metabolic dysfunction⁃associat⁃mal murine model that more closely resembles human MASH progression . Methods: Forty 8 ⁃week⁃old male C57BL/6J mice were randomly assigned to either a control group fed normal chow diet ( NCD) or one of three MASH model groups receiving high⁃fat high⁃cholesterol diet (HFHCD) , choline⁃deficient high⁃fat diet (CDHFD) ,from three randomly selected mice per group were collected for mRNA sequencing ( mRNA⁃seq) analysis . Mean⁃bases . Overlap of functional profiles was analyzed by gene set enrichment analysis (GSEA) profiles to compare the mouse transcriptome with that of human patients at different stages of the disease . Additionally , Pearson ′s correla⁃tion analysis was used to explore the correlation between gene expression of murine models and human MASH . Results: Seven commonly up⁃regulated genes (Col1a1 , Smoc2 , Col6a1 , Gpx3 , Col16a1 , Spp1 and Crtap) were de⁃ways involving steatosis , hepatocellular injury and fibrosis were detected in the three MASH models at the pathway level . HFHCD and MCD might share more common traits . In comparing gene expression and pathway profiles be⁃tween different murine models and patients with different stages of MASH , all three murine MASH models showed a closer resemblance to the human progressive stages of MASH . Notably , the transcriptomic features of the CDHFD model were more consistent with those of human MASH . Conclusion There are certain similarities and differences among the transcriptional profiles of the three MASH models . The MASH models are more similar to the advanced stage of MASH in human patients . Compared to the other two models , the CDHFD model ′ s transcriptome profile more closely resembles human MASH .

Objective:To investigate multi-system involvement in Kennedy′s disease and its association with disease progression.Methods:We retrospectively reviewed the clinical, laboratory, and electrophysiological data from 48 genetically confirmed patients with Kennedy′s disease at the Department of Neurology, First Medical Center of the Chinese PLA General Hospital, between February 2016 and February 2024. The disease progression rate was calculated based on the functional scores at baseline and follow-up. Correlation analyses and multiple linear regression models were employed to assess the relationships among clinical variables and to identify potential predictors of disease progression.Results:The age of muscle weakness onset ranged from 16 to 66 years (mean 42±11 years), with a diagnostic delay of 5.0 (3.0, 9.8) years. Lower limb weakness was the most common initial symptom in 72.9% (35/48) of patients, and 37.5% (18/48) exhibited non-motor manifestations prior to the onset of weakness. Core motor manifestations included bulbar weakness (89.6%, 43/48) and symmetric proximal limb weakness (83.3%, 40/48), frequently accompanied by gynecomastia (74.2%, 23/31) and sexual dysfunction (64.6%, 31/48). The median CAG repeat length was 43 (42, 46), which showed a significant negative correlation with the age at onset ( r=-0.406, P=0.004). Patients with CAG repeats > 43 had a higher prevalence of sexual dysfunction. Elevated serum muscle enzymes were observed in 97.9% (47/48), and abnormal sex hormone levels were detected in 81.2% (39/48). Sensory neuropathy was present in 68.1% (32/47), with CAG repeat length inversely correlating with compound muscle action potential (CMAP) amplitudes in the median ( β=-0.29; t=-2.27, P=0.029) and ulnar ( β=-0.22; t=-2.23, P=0.031) nerves. Low-frequency repetitive nerve stimulation (RNS) revealed a decrement in 43.3% (13/30) of patients, most commonly affecting the axillary and spinal accessory nerves. The disease progression rate was 1.3±0.3 (range: 0.5-2.0). Furthermore, serum creatine kinase-MB (CK-MB) levels were negatively correlated with disease progression rate ( r=-0.303, P=0.036). Conclusions:Kennedy′s disease presents with diverse initial manifestations and frequent multi-system involvement. Non-motor manifestations may precede muscle weakness, serving as valuable clues for early diagnosis. Widespread sex hormone abnormalities (particularly testosterone/luteinizing hormone dysregulation) support the role of androgen insensitivity in disease pathogenesis. Sensory neuropathies are frequent and not length-dependent. The presence of decremental responses on low-frequency RNS suggests neuromuscular junction dysfunction, which may underlie motor impairment in patients with Kennedy′s disease. Finally, serum CK-MB may serve as a potential biomarker for disease progression.

Objective:To detect the expression levels of 12 cytokines in the plasma of patients with primary biliary cholangitis (PBC) and explore their association with PBC disease activity and ursodeoxycholic acid (UDCA) therapeutic response.Methods:This study enrolled 127 patients with PBC who visited Peking Union Medical College Hospital between December 2021 and November 2023 (PBC group) and 32 healthy controls who underwent physical examinations during the same period (control group). The expression of 12 cytokines was measured using flow cytometry, and compared between groups. Spearman correlation analysis was performed to assess the relationship between cytokine levels and five laboratory indicators reflecting PBC disease activity [alkaline phosphatase (ALP), glutamyl transpeptidase (GGT), total bilirubin (TBil), aspartate aminotransferase (AST), and total bile acid (TBA)]. Furthermore, the receiver operating characteristic (ROC) curve analysis was performed to evaluate the effectiveness of cytokines in distinguishing between patients who responded to UDCA treatment and those who did not.Results:The plasma interleukin (IL)-8 levels between the PBC group and healthy controls showed no significant differences, and the plasma IFN-γ levels in PBC patients were significantly higher than those in health controls ( P<0.05). Spearman analysis showed that IL-8 was positively correlated with ALP, GGT, TBil, AST, and TBA ( R2=0.348, 0.401, 0.406, 0.495, 0.417; all P<0.01), and negative correlation was observed between IFN-γand ALP, GGT, and TBA levels ( R2=-0.265, -0.253, -0.232; all P<0.05). The plasma IL-8 level in 52 PBC patients who did not respond to UDCA treatment was significantly higher, while the IFN-γ level was significantly lower than those in 56 PBC patients who responded to UDCA treatment (both P<0.05). ROC analysis showed that the area under the curve for distinguishing plasma IL-8 and IFN-γlevels between PBC patients responding to UDCA treatment and not is 0.631 and 0.783, respectively. The sensitivities were 87.5% and 90.5%, and the specificities were 44.2% and 57.9%, respectively. Conclusion:The levels of plasma IL-8 and IFN-γ are correlated with the disease activity of PBC and can be used to reflect the therapeutic responses to UDCA in PBC patients.

Pediatric rheumatic diseases are a group of complex chronic inflammatory disorders,mainly including juvenile idiopathic arthritis,diffuse connective tissue diseases,systemic vasculitis,and autoinflammatory diseases.Liver involvement is quite common in pediatric rheumatic diseases.In most cases,pediatric rheumatic diseases with liver involvement manifest as varying degrees of abnormal liver enzymes or hepatomegaly and may not have significant liver parenchyma lesions,and such diseases rarely progress to liver decompensation.Only a few children with rheumatic diseases may develop severe liver lesions.Liver involvement in children with rheumatic diseases may be caused by the primary disease itself or concurrent autoimmune liver diseases,but secondary factors are more common,including drug-induced liver damage caused by drugs used to treat rheumatic diseases,viral hepatitis,and fatty liver disease.This article summarizes liver involvement in pediatric rheumatic diseases,in order to provide a reference for the etiological analysis,diagnosis,and treatment strategies of liver involvement in pediatric rheumatic diseases.